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Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma
This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766805/ https://www.ncbi.nlm.nih.gov/pubmed/35071234 http://dx.doi.org/10.3389/fcell.2021.794144 |
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author | Xu, Jiadai Wang, Yue Wei, Zheng Zhuang, Jingli Li, Jing Sun, Yifeng Ren, Liang Wang, Yawen Li, Panpan Gu, Shiyang Zhang, Yian Jiang, Jifeng Chen, Chen Zhang, Yu Liu, Peng |
author_facet | Xu, Jiadai Wang, Yue Wei, Zheng Zhuang, Jingli Li, Jing Sun, Yifeng Ren, Liang Wang, Yawen Li, Panpan Gu, Shiyang Zhang, Yian Jiang, Jifeng Chen, Chen Zhang, Yu Liu, Peng |
author_sort | Xu, Jiadai |
collection | PubMed |
description | This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 [newly diagnosed (ND)] to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages. Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM. |
format | Online Article Text |
id | pubmed-8766805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87668052022-01-20 Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma Xu, Jiadai Wang, Yue Wei, Zheng Zhuang, Jingli Li, Jing Sun, Yifeng Ren, Liang Wang, Yawen Li, Panpan Gu, Shiyang Zhang, Yian Jiang, Jifeng Chen, Chen Zhang, Yu Liu, Peng Front Cell Dev Biol Cell and Developmental Biology This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 [newly diagnosed (ND)] to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages. Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM. Frontiers Media S.A. 2022-01-05 /pmc/articles/PMC8766805/ /pubmed/35071234 http://dx.doi.org/10.3389/fcell.2021.794144 Text en Copyright © 2022 Xu, Wang, Wei, Zhuang, Li, Sun, Ren, Wang, Li, Gu, Zhang, Jiang, Chen, Zhang and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Xu, Jiadai Wang, Yue Wei, Zheng Zhuang, Jingli Li, Jing Sun, Yifeng Ren, Liang Wang, Yawen Li, Panpan Gu, Shiyang Zhang, Yian Jiang, Jifeng Chen, Chen Zhang, Yu Liu, Peng Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
title | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
title_full | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
title_fullStr | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
title_full_unstemmed | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
title_short | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
title_sort | single-cell transcriptomes combining with consecutive genomics reveal clonal evolution and gene regulatory networks in relapsed and refractory multiple myeloma |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766805/ https://www.ncbi.nlm.nih.gov/pubmed/35071234 http://dx.doi.org/10.3389/fcell.2021.794144 |
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